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抗体によって標的にされるSARS-CoV-2のスパイクタンパク質の感染性を高める部位
Yafei Liu1, Wai Tuck Soh2, Jun-Ichi Kishikawa3
1Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
Cell
|June 17, 2021
まとめ
SARS-CoV-2のスパイクタンパク質のN末端領域 (NTD) を標的とする一部の抗体は,ACE2結合を促進することにより,意外にウイルス感染性を高めることができます. この研究は,重症のCOVID-19患者で発見されたNTDの"感染性を高める部位"を特定した.
科学分野:
- ウイルス学
- 免疫学
- 構造生物学
背景:
- SARS-CoV-2のスパイクタンパク質受容体結合領域 (RBD) を標的とする抗体は,ウイルスを中和することが知られている.
- 他のスパイクタンパク質ドメイン,特にN末端ドメイン (NTD) に対する抗体の機能的な影響は,ほとんど未調査のままである.
研究 の 目的:
- RBDを超えた抗スパイク単体抗体の効果を調査する.
- SARS-CoV-2のスパイクタンパク質の特定の抗体標的を特定し,ウイルス感染力またはACE2結合に影響を与える.
主な方法:
- コロナウイルス病 2019 (COVID-19) 患者の単一クローン抗体のスクリーニング.
- 抗体認識部位を特定するための変異分析
- 抗体結合モードを決定する構造分析
- 患者とドナーのサンプルにおける抗体の定量化
主要な成果:
- NTDを標的とした特定の抗体は,オープンなRBDコンフォームを誘発し,ACE2へのスパイクタンパク質結合を強化し,SARS-CoV-2の感染性を高めました.
- NTDの特定の部位は,これらの感染性強化抗体の標的として特定されました.
- これらの増強抗体は重症なCOVID-19患者で多く存在し,未感染者でも低レベルで検出されました.
結論:
- SARS-CoV-2 感染症は,中和する抗体だけでなく,ウイルスの感染性を高める抗体を誘発します.
- 特定されたNTDの感染性強化部位は,ウイルス病原性および免疫反応を理解するための新しい標的を表しています.
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